Nakanishi Shuhei, Vikstedt Riikka, Söderlund Sanni, Lee-Rueckert Miriam, Hiukka Anne, Ehnholm Christian, Muilu Mikko, Metso Jari, Naukkarinen Jussi, Palotie Leena, Kovanen Petri T, Jauhiainen Matti, Taskinen Marja-Riitta
Division of Cardiology, Department of Medicine, University of Helsinki, Helsinki, Finland.
J Lipid Res. 2009 Feb;50(2):183-92. doi: 10.1194/jlr.M800196-JLR200. Epub 2008 Sep 11.
The main antiatherogenic function of HDL is to promote the efflux of cholesterol from peripheral cells and transport it to the liver for excretion in a process termed reverse cholesterol transport. The aim of this study was to evaluate the cholesterol efflux capacity in low- and high-HDL subjects by utilizing monocytes and serum from 18 low-HDL and 15 high-HDL subjects. Low and high HDL levels were defined, respectively, as HDL < or =10(th) and HDL > or =90(th) Finnish age/sex-specific percentile. Cholesterol efflux from [(3)H]cholesterol-oleate-acetyl-LDL-loaded monocyte-derived macrophages to standard apolipoprotein A-I (apoA-I), HDL(2), and serum was measured. In addition, cholesterol efflux from acetyl-LDL-loaded human THP-1 macrophages to individual sera (0.5%) derived from the study subjects was evaluated. Cholesterol efflux to apoA-I, HDL(2), and serum from macrophage foam cells derived from low- and high-HDL subjects was similar. The relative ABCA1 and ABCG1 mRNA expression levels in unloaded macrophages, as well as their protein levels in loaded macrophage foam cells, were similar in the two study groups. Cholesterol efflux from THP-1 foam cells to serum recovered from high-HDL subjects was slightly higher than that to serum from low-HDL subjects (P = 0.046). Cholesterol efflux from THP-1 macrophages to serum from study subjects correlated with serum apoB (P = 0.033), apoA-I (P = 0.004), apoA-II (P < 0.0001), and the percentage of apoA-I present in the form of prebeta-HDL (P = 0.0001). Our data reveal that macrophages isolated from either low- or high-HDL subjects display similar cholesterol efflux capacity to exogenous acceptors. However, sera from low-HDL subjects have poorer cholesterol acceptor ability as compared with sera from high-HDL subjects.
高密度脂蛋白（HDL）的主要抗动脉粥样硬化功能是促进胆固醇从外周细胞流出，并将其转运至肝脏以便在一个称为逆向胆固醇转运的过程中排泄。本研究的目的是通过利用18名低HDL受试者和15名高HDL受试者的单核细胞及血清来评估低HDL和高HDL受试者的胆固醇流出能力。低HDL水平和高HDL水平分别定义为芬兰年龄/性别特异性百分位数中HDL≤第10百分位数和HDL≥第90百分位数。测定了从[³H]胆固醇油酸酯 - 乙酰低密度脂蛋白（LDL）负载的单核细胞衍生巨噬细胞到标准载脂蛋白A - I（apoA - I）、HDL₂和血清的胆固醇流出情况。此外，还评估了从乙酰LDL负载的人THP - 1巨噬细胞到源自研究受试者的个体血清（0.5%）的胆固醇流出情况。低HDL和高HDL受试者来源的巨噬细胞泡沫细胞向apoA - I、HDL₂和血清的胆固醇流出情况相似。两个研究组中未负载巨噬细胞中相对ATP结合盒转运蛋白A1（ABCA1）和ATP结合盒转运蛋白G1（ABCG1）mRNA表达水平以及负载巨噬细胞泡沫细胞中的蛋白水平相似。从THP - 1泡沫细胞到从高HDL受试者回收的血清的胆固醇流出略高于到低HDL受试者血清的胆固醇流出（P = 0.046）。从THP - 1巨噬细胞到研究受试者血清的胆固醇流出与血清载脂蛋白B（apoB）（P = 0.033）、apoA - I（P = 0.004）、apoA - II（P < 0.0001）以及以前β - HDL形式存在的apoA - I百分比（P = 0.0001）相关。我们的数据表明，从低HDL或高HDL受试者分离出的巨噬细胞对外源受体显示出相似的胆固醇流出能力。然而，与高HDL受试者的血清相比，低HDL受试者的血清具有较差的胆固醇受体能力。
